Drug eluting vascular closure devices and methods

ABSTRACT

Drug eluting vascular closure devices and methods for closing a blood vessel puncture site disposed at a distal end of a tissue tract are described. The devices and methods rely on a combination of the body&#39;s own natural mechanism to achieve hemostasis with bio-chemical agents to accelerate the hemostatic process. One method includes the steps of introducing a closure device through the tissue tract and deploying an expansible member at a distal end of the device within the blood vessel to occlude the puncture site. A bio-chemical sealing member disposed proximal the expansible member is then displaced so as to expose a bio-chemical region or release region of the device. At least one bio-chemical agent is thereafter released from the device and into the tissue tract to accelerate the occlusion process in the tract.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to devices and methods forpercutaneous sealing of puncture sites in body lumens or tissue tracts.More specifically, the present invention relates to drug elutingvascular closure devices and methods for hemostasis of vascular puncturesites.

Percutaneous access of blood vessels in the human body is routinelyperformed for diagnostics or interventional procedures such as coronaryand peripheral angiography, angioplasty, atherectomies, placement ofvascular stents, coronary retroperfusion and retroinfusion, cerebralangiograms, treatment of strokes, cerebral aneurysms, and the like.Patients undergoing these procedures are often treated withanti-coagulants such as heparin, thrombolytics, and the like, which makethe closure and hemostasis process of the puncture site in the vesselwall at the completion of such interventional procedures more difficultto achieve.

Various devices have been introduced to provide hemostasis, however nonehave been entirely successful. Some devices utilize collagen or otherbiological plugs to seal the puncture site. Alternatively, suturesand/or staples have also been applied to close the puncture site.External foreign objects such as plugs, sutures, or staples however maycause tissue reaction, inflammation, and/or infection as they all “leavesomething behind” to achieve hemostasis.

There is also another class of devices that use the body's own naturalmechanism to achieve hemostasis wherein no foreign objects are leftbehind. Such devices typically provide hemostasis by sealing thepuncture site from the inside of the vessel wall wherein the device isleft in place in the vessel lumen until hemostasis is reached andthereafter removed. Although such safe and simple devices have achievedrelative levels of success, they often are slow in achieving completehemostasis, particularly in highly anti-coagulated patients. As such,such devices are often used as an adjunct to manual compression whichstill remains to be the most used method in closing the puncture siteafter the interventional procedure.

There is yet another class of devices where highly thrombogenicsubstances are mixed and injected to the puncture site for the purposeof accelerating the hemostatic process. These mixtures contain one ormore clot promoting substances, such as thrombin and/or fibrinogen,along with other substances, such as collagen. These devices generallywork by first occluding the puncture site from the inside of the vessel,usually by use of a balloon, and then injecting the mixture into thetissue tract. The balloon is then removed. Such devices suffer fromseveral drawbacks which may cause severe complications. For example, theoccluding member may not be adequate to prevent these highlythrombogenic substances from entering the blood vessel. Further, theinjection of the mixture is often not well controlled and highlytechnique dependant, which again may allow these substances to enter theblood stream.

In light of the above, it would be desirable to provide alternativedevices and methods for providing complete hemostasis of a puncture sitein a body lumen, particularly blood vessels of the human body. It wouldbe particularly desirable if such devices and methods utilize the body'sown natural healing mechanism to achieve hemostasis. It would be furtherdesirable if the natural hemostatic process can be safely accelerated bythe controlled use of biochemical agents. It would be further desirableif such devices and systems utilize a simple construction and userinterface allowing for convenient application without numerousintermediary steps. Further, such devices should be safe and reliablewithout the need for much user intervention. At least some of theseobjective will be met by the devices and methods of the presentinvention described hereinafter.

2. Description of the Background Art

Hemostasis devices for use in blood vessels and tracts in the body aredescribed in pending U.S. patent application Ser. Nos. 10/974,008;10/857,177; 10/821,633; 10/795,019; and 10/718,504 and U.S. Pat. Nos.6,656,207; 6,464,712; 6,056,770; 6,056,769; 6,045,570; 6,022,361;5,951,589; 5,922,009; and 5,782,860, assigned to the assignee of thepresent application. The following U.S. Patents and Publications may berelevant to the present invention: U.S. Pat. Nos. 4,744,364; 4,852,568;4,890,612; 5,108,421; 5,171,259; 5,258,000; 5,383,896; 5,419,765;5,454,833; 5,626,601; 5,630,833; 5,634,936; 5,728,134; 5,836,913;5,861,003; 5,868,778; 5,951,583; 5,957,952; 6,017,359; 6,048,358; and6,296,657; U.S. Publication Nos. 2002/0133123; 2003/0055454;2003/0045835; and 2004/0243052.

The full disclosures of each of the above mentioned references areincorporated herein by reference.

BRIEF SUMMARY OF THE INVENTION

The present invention provides drug eluting, self-tensioning closuredevices and methods for percutaneous access and closure of puncturesites in a body lumen, particularly blood vessels of the human body. Itwill be appreciated however that application of the present invention isnot limited to the blood vasculature, and as such may be applied to anyof the vessels, even severely tortuous vessels, ducts, and cavitiesfound in the body as well as tissue tracts. Such closure devices andmethods utilize the body's own natural healing mechanism to achievehemostasis. This natural hemostatic process is further accelerated bythe integration of bio-chemical agents or means for delivering suchagents.

In a first aspect of this invention, a device for closing a blood vesselpuncture site disposed at a distal end of a tissue tract comprises ashaft having a proximal end and a distal end, an expansible member, abio-chemical sealing member, and a bio-chemical region or releaseregion. The shaft is configured to advance through the tissue tractwhile the expansible member disposed on the distal end of the shaft isdeployable within the blood vessel. The bio-chemical sealing member isslidably disposed over the shaft and proximal the expansible member. Thebio-chemical region or release region is disposed under the sealingmember. Advantageously, displacement of the biochemical sealing memberin a proximal direction exposes the region so as to allow for safe andcontrolled release of bio-chemical agents into the tissue tract forenhanced and complete hemostasis of the puncture site.

The bio-chemical sealing member prevents severe complications as aresult of bio-chemical agents from coming in contact with the bloodstream by only allowing for the controlled exposure of such agents inthe tissue tract. The sealing member has a length in a range from about0.1 cm to about 100 cm, typically from about 5 cm to about 20 cm and adiameter in a range from about 0.5 mm to about 5 mm, typically fromabout 1 mm to about 3 mm. The sealing member may be a tubular memberformed from a variety of medical grade materials, including coiledstainless steel tubing or polymer materials such as nylon, polyurethane,polyimide, PEEK®, PEBAX®, and the like.

In a preferred embodiment of the device, a tensioning element, such as aspring or coil, is further provided. The tensioning element is slidablydisposed over the shaft and under the sealing member proximal theexpansible member. Generally, during application of the device, thetensioning element is preferably positionable in the tissue tract, butin other instances may be outside the tissue tract. The tensioningelement gauges how much tension is being applied to the expansiblemember as it is seated against the puncture site so as to prevent a userfrom applying excessive force on the device causing undesirable movement(e.g., device is pulled out of patient body). The tensioning elementalso provides device compliance in cases of patient movement while thedevice is in place. The expansible member allows for sealing of thepuncture site while the tensioning element along with an external clipapply and maintain tension to the expansible occluder so that it isseated against the puncture site at a vascular surface (e.g., bloodvessel wall).

Positioning the expansible member against the vessel wall positions thebio-chemical region or release region outside the vessel lumen at apredetermined distance from the vessel wall and proximal the expansiblemember. Therefore, the expansible member provides not only occlusion atthe vessel puncture site but also functions as a locator so as toposition the bio-chemical region or release region outside the vessellumen. This in turn ensures safe release of bio-chemical agents in thetissue tract and outside the blood stream. The predetermined distance isin a range from about 0 to about 20 mm, typically in a range from about2 mm to about 10 mm.

The bio-chemical region or release region has a length in a range fromabout 1 mm to about 100 mm, typically in a range from about 5 mm toabout 50 mm. It will be appreciated that the length and/or volume of theregion may be varied in order to integrate and release the desiredamount of bio-chemical agent. In one embodiment, the bio-chemical regionincludes at least one bio-chemical agent disposed on the distal end ofthe shaft proximal the expansible member and distal the tensioningelement. In another embodiment, the region includes at least onebio-chemical agent disposed on the tensioning element. The agents may becoated, sprayed, molded, dipped, vapor deposited, plasma deposited, orpainted thereon. Such a bio-chemical region on the occlusion deviceitself further minimizes variations due to user techniques, which may beparticularly problematic with injection protocols where such agents areinjected into the tract by the user. In yet another embodiment, thedevice may further incorporate an expansible feature disposed on thedistal end of the shaft proximal the expansible member, wherein theregion includes at least one bio-chemical agent associated with theexpansible feature.

In alternative embodiments of the present invention, the device mayfurther incorporate at least one bio-chemical delivery conduit disposedover the shaft and under the tensioning element and a bio-chemicalinjection port in fluid communication with the delivery conduit. Theinjection port may be connected to a syringe by use of a compressionfitting or with an integrated luer lock. The bio-chemical agents areinjected into the device via the syringe once the device is properlypositioned. It will be appreciated that the size of the injection portand the delivery conduit may be selected to control the delivery rate ofsuch agents. In one example, the release region includes at least oneopening, aperture, or orifice in fluid communication with a distal endof the conduit proximal the expansible member. It will be appreciatedthat any number, size, and/or shape of opening(s) may be utilized inorder to obtain the desired release rate of bio-chemical agent. Therelease region may incorporate about 1 opening to about 100 openings,typically about 1 opening to about 10 openings. In another example, therelease region includes at least one porous member in fluidcommunication with a distal end of the conduit proximal the expansiblemember so as to allow for the desired release of the bio-chemical agent.

A controlled delivery rate allows the bio-chemical agents to “ooze” outof the release region. This may eliminate the potential of high pressurerelease, which in turn minimizes the possibility of these agents fromentering the blood stream. In addition, the sealing member serves tocover the bio-chemical release region so as to prevent any blood fromflowing back through the release region, through the delivery conduit,and out through the injection port. The sealing member is only slidablydisplaced, revealing the bio-chemical release region, when it isdesirable to deliver the bio-chemical agents.

The device of the present invention may further incorporate a spacerelement disposed between the sealing member and the tensioning elementso that the sealing member may easily slide over the tensioning element.The spacer element may be a tubular member formed from a variety ofmaterials, including tubular polymer materials such as nylon,polyurethane, polyimide, PEEK®, PEBAX®, and the like. The device furtherincludes a handle on a proximal end of the shaft. A safety tab may bedisposed between the handle and the sealing member. The safety tabprevents any undesirable displacement of the sealing member so as toinhibit inadvertent release of bio-chemical agents.

The present invention integrates the expansible member, bio-chemicalsealing member, bio-chemical region or release region, and tensioningelement in a single unitary catheter construction. This simpleconstruction and user interface allows for safe, easy and convenientapplication of the device without numerous intermediary steps. Thesealing member in combination with the locating expansible memberensures that the bio-chemical region or release region is only exposedin the tissue tract. This results in a more reliable, safe, andeffective device which provides immediate and complete hemostasis, whichin turn reduces the risk of bleeding, hematoma formation, thrombosis,embolization, and/or infection.

In another aspect of the present invention, methods for hemostasis of apuncture site in a blood vessel at a distal end of a tissue tract areprovided. One method comprises introducing any one of the closuredevices as described herein through the tissue tract. The expansiblemember is deployed at a distal end of the device within the bloodvessel. The bio-chemical sealing member disposed proximal the expansiblemember is then displaced once properly positioned so as to expose abio-chemical region or release region of the device. At least onebio-chemical agent is then released from the device and into the tissuetract.

The sealing member is displaced in a proximal direction so as to exposeat least a portion of the region. This displacement distance is in arange from about 0.1 cm to about 10 cm, typically from about 0.5 cm toabout 5 cm. The method further comprises deploying the tensioningelement disposed proximal the expansible member within the tissue tractso that the expansible member is seated against a puncture site.Typically, deploying the tensioning element and displacing the sealingmember is carried out simultaneously so as to provide for easy andconvenient application of the device without numerous intermediarysteps. However, it will be appreciated that deployment of the tensioningelement may be carried out independently, typically prior todisplacement of the sealing member, so as to provide for properpositioning of the region or release region within the tissue tract andclosure of the puncture site.

The amount of tension applied to the expansible member by the tensioningcoil or spring is in the range from about 0.5 ounce to 30 ounces,typically in a range from about 2 ounces to 10 ounces. As describedabove, the expansible member locates and closes the puncture site in theblood vessel wall. Coil elongation is sufficient to provide adequateamount of tension on the expansible member to temporary seal thepuncture and to adequately displace the sealing member to reveal thebio-chemical region or release region. In some embodiments, coilelongation may be limited by a coupling member. Generally the amount ofelongation of the tensioning coil may be the same as for displacement ofthe sealing member. The tension provided by the tensioning coil and theexposure of the bio-chemical agents may be maintained by application ofan external clip on the tensioning coil, generally over the sealingmember, wherein the clip rests over the skin at the puncture site.

Bio-chemical agent release generally comprises positioning the region ata predetermined distance proximal to the expansible member and outsidethe blood vessel wall. In particular, increasing the tension in the coilpositions the expansible member against the puncture site and locatesthe bio-chemical region or release region in the tissue tract at thepredetermined distance. Further increase in tension will cause thesealing member to disengage from an attachment point at the proximal endof the expansible member and the tensioning coil to elongate. Elongationof the tensioning coil will result in the sealing member to slideproximally so as to expose the region to the surrounding tissue forrelease of the bio-chemical agent.

The bio-chemical agents may accelerate the coagulation process andpromote the formation of coagulum at the puncture site so to achievecomplete hemostasis. The bio-chemical agent may comprise a variety ofagents including clot promoting agents (e.g., thrombin, fibrinogen,etc.) or vaso-constricting agents (e.g., epinephrine, etc.). Thebio-chemical agent is released for a time period in the range from about0.1 minute to about 15 minutes, typically from about 0.5 minute to about5 minutes. As described above, the occlusion device may be modified inseveral ways (e.g., region length, region volume, release regionopenings, conduit dimensions, number of conduits, or port dimensions) toachieve the desired bio-chemical agent release characteristics (e.g.,rate, amount, time, etc.). The methods of the present invention mayinvolve re-hydrating the bio-chemical agent with fluid in the tissuetract so as to generate coagulum. These agents may use the bloodcomponents to form a coagulum even at the presence of anti-coagulants.

As described above, the bio-chemical agent may be coated, sprayed,molded, painted, dipped, or deposited at the region. Alternatively,bio-chemical agents may be injected in a delivery conduit in fluidcommunication with at least one opening disposed at the release region.The sealing member in such an embodiment further prevents any blood fromflowing back through the openings of the release region prior to placingthe expansible member against the vessel wall when the release region isin the vessel lumen. Injection of bio-chemical agents in the presence ofblood in the bio-chemical delivery pathway may cause undesirablecoagulum to form in the pathway which could prevent the bio-chemicalagents from reaching the target site.

A further understanding of the nature and advantages of the presentinvention will become apparent by reference to the remaining portions ofthe specification and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings should be read with reference to the detaileddescription. Like numbers in different drawings refer to like elements.The drawings, which are not necessarily to scale, illustratively depictembodiments of the present invention and are not intended to limit thescope of the invention.

FIG. 1 illustrates a first embodiment of a drug eluting, self-tensioningvascular closure device for hemostasis of vascular puncture sitesconstructed in accordance with the principles of the present invention.

FIG. 2 illustrates an exploded view of the bio-chemical region on thedistal end of the device of FIG. 1.

FIG. 3 illustrates the device of FIG. 1 in an expanded configurationwith the occluding member deployed.

FIG. 4 illustrates the device of FIG. 1 in an expanded configurationwith the occluding member under tension after removal of the safety sealand with the bio-chemical sealing member displaced proximally so as toexpose the contents of the bio-chemical region.

FIGS. 5A through 5F illustrate a method for hemostasis of a puncturesite in a body lumen employing the device of FIG. 1.

FIG. 6 illustrates a second embodiment of a drug eluting,self-tensioning vascular closure device for hemostasis of vascularpuncture sites constructed in accordance with the principles of thepresent invention.

FIG. 7 illustrates an exploded view of the bio-chemical injection portand delivery conduit of the device of FIG. 6.

FIG. 8 illustrates an exploded view of the bio-chemical release regionon the distal end of the device of FIG. 6.

FIG. 9 illustrates the device of FIG. 6 in an expanded configurationwith the occluding member deployed.

FIG. 10 illustrates the device of FIG. 6 in an expanded configurationwith the occluding member under tension and with the bio-chemicalsealing member displaced proximally so as to expose the bio-chemicalrelease region so that attachment of a syringe to the bio-chemicalinjection port provides delivery of bio-chemical agents.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to FIG. 1, a first embodiment of a drug eluting,self-tensioning vascular occlusion device 70 for hemostasis of vascularpuncture sites is illustrated, wherein at least one bio-chemical agent152 is integrated with the device in a bio-chemical region or chamber151. Device 70 generally comprises a first flexible elongated tubularmember 71 formed from coiled stainless steel tubing or polymer materialssuch as nylon, polyurethane, polyimide, PEEK®, PEBAX®, and the like.Tubular member 71 may have a length in a range from about 5 cm to about50 cm, typically in the range from about 10 cm to about 30 cm and adiameter in the range from about 0.25 mm to about 5 mm, typically in therange from about 0.5 mm to about 2 mm. An expansible occlusion member 74is disposed on the distal end of tubular member 71. A bio-chemicalsealing member 153 is slidably disposed over the tubular member 71 andproximal the expansible member 74. The bio-chemical region 151containing the bio-chemical agent 152 is disposed under the sealingmember 153. It will be appreciated that the above depictions are forillustrative purposes only and do not necessarily reflect the actualshape, size, or dimensions of the device 70. This applies to alldepictions hereinafter.

The expansible member 74 may be formed from a variety of medical gradematerials, including stainless steel, superelastic material such asNITINOL®, or polymer materials such as nylon, polyurethane, polyimide,PEEK®, PEBAX®, and the like. Preferably the expansible member 74 is madeof superelastic NITINOL® material. The expansible member 74 in aretracted or collapsed state has a diameter of less than about 3 mm,preferably less than about 1.5 mm, as shown in FIGS. 1 and 2. Whendeployed, the expansible member 74 in an expanded state has a diameterin a range from about 3 mm to about 20 mm, preferably from about 3.5 mmto about 8 mm, as shown in FIGS. 3 and 4. Exemplary expansiblestructures 74 are described in detail in co-pending U.S. patentapplication Ser. No. 10/718,504. Still further embodiments of a braidedmesh member 74 are described in U.S. Pat. No. 5,836,913.

The expansible member 74 may at least partially or preferably be fullycovered with an elastomeric membrane material 96. Membrane 96 may beformed from a variety of medical grade materials, such as thermoplasticelastomers (e.g., CHRONOPRENE® or POLYBLEND®) having durometers in arange from 15 Å to about 40 Å. Membrane 96 may be connected at a distalconnection point 77 and a proximal connection point 75. Adhesives suchas LOCTITE® 4014 may be used to attach membrane 96 to the expansiblemember 74 and catheter shaft 71. Alternatively, membrane 96 may take aform of a sock having its distal end sealed through a heat stake processor the like. In this case membrane 96 may not have to be attacheddistally. Membrane 96 preferably has a diameter that is sufficient tocover the expansible member 74. In some embodiments, membrane 96 may bedesigned and attached to facilitate expansible member deployment as wellas to reduce the amount of required elongation when the expansiblemember 74 is deployed. This may be achieved by molding the membrane 96so that its midpoint diameter, where deployed expansible member 74 hasits greatest diameter, is larger than its proximal and distal enddiameters (e.g., a spherical shape). Membrane 96 may also be formed likea tube with a larger diameter than needed (e.g., diameter of retractedexpansible member 74), and then stretched over expansible member 74 andattached. The stretch should be enough to reduce the diameter of themembrane 96 to that of the expansible member 74. In such a case, whenmember 74 is deployed, there is less elongation and stress experiencedby membrane 96. The membrane 96 may additionally form a membrane tip ata distal end of catheter 70 so as to provide a soft and blunt point forpercutaneous access.

Referring now to FIG. 2, the bio-chemical agents 152 may be composed ofclot promoting agents such as thrombin and fibrinogen and/orvaso-constrictors such as epinephrine. These agents 152 may take on aform of a powder, paste that can be applied to the biochemical chamberor region 151. Alternatively, such agents 152 may be molded in a form ofa cylindrical tube with a longitudinal central hole that can be slidablydisposed over member 71 and positioned between fixed attachment members75 and 150 in the assembly process. The bio-chemical chamber/region 151is located between the proximal end of member 75 and distal end ofattachment member 150. The length of region 151 determines the amount ofbio-chemical agents 152 that can be integrated with the device, as wellas the extent of the exposure of such agents to the tissue. It shouldalso be noted that by increasing the outside diameters of members 75 and150, the volume of chamber 151 can be increased and hence the volume ofthe bio-chemical agents 152 incorporated with the device.

The bio-chemical sealing member 153 generally comprises a flexibleelongated tubular member. In a preferred embodiment, the tubular member153 may have a length that extends from attachment member 75, andoverlapping member 75, to grip member 85, partially or fully overlappingmember 85. The inside diameter of member 153, at least at the distalend, is similar to the outside diameter of member 75. Member 153 isslidably positioned, at least partially, over member 75. The interactionof members 153 and 75 provide for a fluid tight barrier so that bloodwill not come in contact with the bio-chemical agent prior to theintended time.

In the preferred embodiment of the present invention, a tensioningelement 86 is slidably disposed over the tubular member 71 and proximalthe expansible member 74. the tensioning coil 86 is attached to thetubular member 71 with attachment member 150. Member 150 may be in atubular form and made from stainless steel tubing or polymer materialssuch as nylon, polyurethane, polyimide, PEEK®, PEBAX®, and the like.Coil 86, attachment member 150 and tubular member 71 are connectedtogether by use of epoxy. The attachment point may be from 1 mm to 100mm proximal to the member 75, preferably in the range of 5 mm to 50 mm.The tensioning element 86 is described in more detail in co-pending U.S.patent application Ser. No. 10/974,008.

The function of bio-chemical seal 153 is to provide a barrier betweenthe bio-chemical agents 152 and bodily fluids such as blood, and onlyallow the exposure of such agents to the tissue when the device is incorrect position and the operator chooses to do so. Exposure of thebio-chemical region 151 to the surrounding tissue happens when thetensioning coil 86 is grabbed at grip member 85 and is pulled proximallywith respect to member 75 to apply tension to the deployed expansiblemember 74 at the puncture site. The proximal pull of grip member 85causes the tensioning coil 86 to elongate. The seal member 153 isattached to the coil 86 and grip member 85. Since member 153 is notstretchable, the elongation of coil 86 results in disengagement of thedistal end of member 153 from member 75. Seal 153 slides proximally overthe bio-chemical chamber/region 151 and exposes the bio-chemical agents152 to the surrounding tissue. A spacer 154 provides adequate spacebetween coil 86 and sealing member 153, so that member 153 can easilyslide over coil 86. It should be noted that coil 86 elongation happensas the result of interference of the occluding expansible member 74 withthe vessel wall at the puncture site. This in turn slides the sealingmember 153 proximally, exposing the bio-chemical agents 152 in thetissue tract where it is needed.

It will be appreciated that bio-chemical seal 153 may be constructed tofunction independently from the tensioning coil 86. Also, in someembodiments, a length of coil 86, or the entire length of coil 86 may becoated with the bio-chemical agent 152. In such case, when coil spring86 is elongated to provide tension to the expansible member 74, thedeformation of the elongating coil spring 86 may result in breaking offof the agents 152 from the coil. This may result in faster re-hydrationof the bio-chemical agents 152 and consequently acceleration of thecoagulation process in the tract. Still further, the bio-chemicalchamber 151 of device 70 may include an expansible feature over whichthe bio-chemical agent 152 is dispensed (e.g., coated). When desirable,this expansible member which may take the form of a balloon or a braidedmesh, can be expanded, resulting in the agents 152 breaking off in thesurrounding tissue, and hence accelerating the bio-chemical reaction.

The device 70 of the present invention may further incorporate a safetyseal 155 to prevent inadvertent release of bio-chemical agents 152 bypreventing coil 86 from sliding over member 71. Safety seal 155 may bemade of different materials and be implemented in different fashions.One such implementation may take the form of heat shrinkable tubing. Thetubing may be shrunk over member 71 to the proximal end of the coil 86or preferably overlapping grip member 85. To remove the safety seal withease, seal 155 may have a tab 156 that may be easily grabbed and pulled,tearing the safety seal 155 along the length of member 71. Removal ofthe safety seal 155 would allow coil 86 to freely slide over tubularmember 71, exposing the bio-chemical agents 152 to the surroundingtissue.

The bio-chemical agent 152 is sealed from coming in contact with thecirculating blood and generally is released in the tissue tract in thefascia at the puncture site. During device application, the expansiblemember 74 will be positioned and anchored against the puncture site inthe vessel lumen. In particular, the expansible member 74 allows forsealing of the puncture site and locating the bio-chemical agents 152appropriately in the tissue tract. The tensioning element 86 applies andmaintains tension to the expansible occluder 74 while the sealing member153 simultaneously reveals the biochemical agents 152 to bring suchagents in contact with the surrounding tissue to accelerate the processof hemostasis.

Referring now to FIGS. 3 and 4, a proximal end of the device 70comprises deployment means 78. Deployment of the expansible member 74typically comprises pushing or pulling the two part handle assembly 78coupled to the expansible member 74. A proximal end of handle assembly78 comprises an actuating assembly 101 which is coupled to a push/pullmember 76. Proximal movement of assembly 101 relative to a grip handle102 deploys the expansible member 74. The grip handle 102 comprises atubular member 103 formed from suitable metal tubing (e.g., stainlesssteel) or polymer materials (e.g., polyurethane, polyimide, PEEK®,PEBAX®, and the like). Member 103 is coupled to the catheter shaft 71 bymeans of an expander element 104 so as to account for the difference inan outside diameter of catheter 71 and an inside diameter of member 103.Elements 71, 103, and 104 may be attached by the use of adhesives.Member 103 further includes a feature 105, such as an indentation from acrimping process when element 103 is formed from a stainless steel orother metallic hypotube. Indentation 105 provides interference toelement 106 of the actuating assembly 101.

Actuating assembly 101 further includes a tubular member 107 that isattached to the push/pull member 76 by a crimp process and/or adhesive.Member 107 provides added stiffness to the actuating mechanism 101 aswell as provides for a larger surface area that consequently allows forenhanced adhesion of elements 106, 108, and 109 to member 107. Theseelements may comprise individual, separate parts, preferably formed frompolymer materials such as polyurethane, polyimide, PEEK®, PEBAX®, andthe like. These elements may be optionally incorporated into element 107through an over molding process. Once the device 70 is deployed,interference of detent element 106 with indentation 105 securelymaintains the expansible member 74 in its deployed position as shown inFIGS. 3 and 4. A proximal end of detent 106 may have a shallow angle inrelation to the catheter shaft 71 so as to provide simplified deploymentof the expansible member 74. A distal end of detent 106 may be moreperpendicular to the catheter shaft 71 so as to provide moreinterference to feature 105, thereby requiring greater force to undeploythe expansible member 74. The increased undeployment force is desirableto avoid inadvertent device collapse. Optionally, indentation 105 may bedesigned so that a distal side of the feature has a much shallower anglein relation to the catheter shaft 71 than a proximal side.

Elements 108 and 109 primarily provide support and alignment of theactuating assembly 101. Element 109 may be formed from a bright distinctcolor to indicate when the expansible member 74 is deployed. Element 110comprises a tubular member, preferably having the same outer diameter asmember 103. A distal end of tubular member 110 abuts a proximal end ofmember 103 so as to provide a positive stop to the movement of theactuating assembly 101 during the undeployment of the expansible member74. Cap 111 at the most proximal end of the device 70 provides a softtip for easier undeployment of expansible member 74. Cap 111 may beformed from rubber or similar materials.

In operation, handle assembly 78 is held by grabbing onto element 103with one hand and element 110 with the other hand. Element 110 is thenpulled in a proximal direction while holding element 103 stationary. Aselement 110 is pulled back, detent 106 slides over indentation 105 untilit is completely moved to the proximal side of feature 105. FIGS. 3 and4 illustrate the expansible member 74 that is in the form of a tubularbraided mesh in the deployed and expanded state. The interferencebetween elements 105 and 106 keeps the expansible member 74 in thedeployed configuration. Undeployment of the device 70 may be effectedwith a single hand. In particular, member 103 may be grabbed by the palmof the hand while the thumb presses on cap 111. This causes theactuating mechanism 101 to move forward and the detent member 106 toslide distally over feature 105 resulting in the retraction of theexpansible member 74.

Referring now to FIGS. 5A through 5F, a method for hemostasis of apuncture site in a body lumen employing the device 70 of FIG. 1 isillustrated. FIG. 5A depicts an existing introducer sheath 40 advancedthrough an opening in a skin surface 46, tissue tract in fascia 45 andvessel wall 43 and seated in a vessel lumen 41 at the completion of acatheterization procedure. Device 70 is then inserted through the hub ofthe sheath 40 and is advanced until the expansible member 74 is outsidethe sheath 40 and in the vessel lumen 41, as shown in FIG. 5B. Thispositioning may be indicated by a mark or feature on the catheter 71 orthe handle assembly 78.

As shown in FIG. 5C, the expansible member 74 is then deployed byoperation of the handle assembly 78. The sheath 40 is then slowly pulledout of the body, placing the expansible member 74 against the inner wallof the vessel 43 at the puncture site 42. As the sheath 40 is removed,the grip member 85 which is slidably disposed over the catheter shaft 71and the handle assembly 78 are revealed. Sheath 40 is then discarded,leaving deployed expansible member 74 seated at the puncture site 42 andthe bio-chemical chamber/region 151 in the tissue tract 47 as shown inFIG. 5D. If the device is equipped with the safety seal 155 as in device70, then the safety seal 155 is removed by pulling the tab 156proximally along the catheter shaft.

Referring now to FIG. 5E, once safety seal 155 is removed, the gripelement 85 is grabbed and pulled in a proximal direction. Grip 85 ismoved proximally to provide adequate amount of tension to the deployedexpansible member 74 to achieve hemostasis. Typically, the amount oftension applied to the expansible member 74 is in the range of 0.5ounces to 30 ounces. In particular, proximal movement of grip 85 causessimultaneous elongation of the tensioning coil 86, causing theexpansible member to locate and close the puncture site 42, anddisplacement of the bio-chemical seal 153, exposing the bio-chemicalagent 152 to the surrounding tissue at a predetermined distance from thepuncture site. The elongated position of coil 86 is maintained byapplication of a small external clip 50 to the catheter and seatedagainst the surface of the skin 46, as shown in FIG. 5E. Device 70 isleft in this position for a period of time to allow the bio-chemicalagent 152 to reconstitute with the fluids in the tissue tract 47,generating coagulum. Clip 50 is then removed and the expansible member74 is collapsed by manipulation of the handle assembly 78. Device 70 isthen removed, leaving the active bio-chemical agents 152 and thecoagulum in the tract 47 and adjacent the vessel puncture site 42, asshown in FIG. 5F. Additional finger pressure at the puncture site may berequired to allow the coagulum to seal the small hole left in the vesselwall after removal of the device.

Referring now to FIG. 6, another embodiment of an exemplary drugeluting, self-tensioning vascular occlusion device 80 for hemostasis ofvascular puncture sites is illustrated, wherein the bio-active agents152 may be stored separately and safely injected into the target sitethrough a bio-chemical release region 163 once the device is properlypositioned. The bio-chemical delivery system of device 80 is composed ofan elongated tubular member 160. Member 160 may be coaxially locatedover member 71 as shown in FIG. 6. 160 has an inside diameter that islarger than the outside diameter of member 71. Member 160 is formed fromcoiled stainless steel tubing or polymer materials such as nylon,polyurethane, polyimide, PEEKS, PEBAX®, and the like. The gap madebetween the inside of member 160 and the outside of member 71 definesthe bio-chemical delivery conduit 161.

Referring now to FIG. 8, the distal end of member 160 has a plurality ofopenings 162 defining the bio-chemical release region 163. Openings 162vary in number and may be from 1 opening to 100 opening, preferably from1 opening to 10 openings. The size, shape, and/or number of openings 162determines the rate of the release of the bio-chemical agents into thesurrounding tissues. Alternatively, the bio-chemical release region 163may not be part of member 160, and may be a separate member, made ofporous material which is in fluid communication with member 160. Ineither embodiment, release region 163 is located at a predetermineddistance proximal to the expansible member 74.

Referring now to FIG. 7, a bio-chemical injection port 164 isillustrated. Port 164 comprises a flexible elongated tubular member thattransitions to member 160 at its distal end by means of a couplingmember 165. At a proximal end, the port 164 provides a coupling to asyringe 167 for the injection of bio-chemical agents 152. Members 164and 165 may be constructed from stainless steel tubing or polymermaterials such as nylon, polyurethane, polyimide, PEEK®, PEBAX®, and thelike. Member 165 may or may not be a flexible member. Member 165preferably has an outside diameter that is not larger than the outsidediameter of the handle assembly 78. This ensures that device 80 can gothrough the existing sheath 40 without interference, as was describedfor device 70 in FIGS. 5A through 5F. Coupling member 165 is connectedto member 160 via member 166. Members 164, 165 and 160 are attached bymeans of epoxy to provide a fluid tight seal at attachment points 166.

It will be appreciated that the drug delivery conduit 160 may comprise asingle or multiple elongated tubular member(s) of varying length(s) thatrun(s) along the length of member 71. At a proximal end, these conduitscouple into delivery port 164 via coupling member 165. At a distal end,these tubular members may terminate at different points proximal to theexpansible member 74, dispersed over release region 163. Distally, theseconduits may have at least one opening for the release of thebio-chemical agents into the region.

The bio-chemical sealing member 153 of device 80 functions in a similarfashion as in device 70. In addition, the sealing member 153 of device80 prevents blood from flowing back through the bio-chemical deliverpath 163, 162, 161, 164. However, it will be appreciated that the backflow of blood through the bio-chemical delivery pathway may be used asan indicator that the bio-chemical release region 163 is in the vessellumen. When the back flow stops, that may be an indication that therelease region 163 is in the tissue tract, where there is no appreciableblood pressure. In addition to the expansible member 74, this featuremay add more certainty to the positioning of the bio-chemical releaseregion 163 and hence improve safety. In such case, prior to injection ofthe bio-chemical agents 152, the pathway may be flushed with solutionssuch as saline.

The tensioning coil 86, spacer element 154, and grip member 85 of device80 function in a similar fashion as in device 70. In device 80, however,the elongation of tensioning coil 86 is limited by the distal end ofcoupling member 165 at attachment point 166. The distance between theproximal end of the coil spring 86 and the distal end of coupling member165 at point 166 is long enough to provide the adequate amount oftension. This distance is also sufficient to allow the bio-chemical seal153 to move proximally to expose the entire bio-chemical release region163. FIG. 9 illustrates device 80 with a deployed expansible member 74.FIG. 10 illustrates device 80 when the coil 86 is elongated to applyadequate amount of tension to expansible member 74 and to expose thebio-chemical release region 163. The attachment of syringe 167 todelivery port 164 for delivery of bio-chemical agents 152 to the targetsite is also illustrated.

In operation, device 80 is inserted through the sheath 40 and advanceduntil the expansible member 74 is out of the sheath 40 and in the bloodvessel 41. The expansible member 74 is deployed by manipulation of thehandle assembly 78, the sheath 40 is removed and discarded, and thedeployed expansible member 74 is placed against the inside wall of thevessel at the puncture site 42. Tension is then applied by proximallysliding grip member 85 of coil 86. The applied tension at the deployedexpansible member 74 will provide hemostasis, and locates bio-chemicalrelease region 163. Elongation of the coil 86 reveals the bio-chemicalrelease region 163 to the surrounding tissue tract 47. The tension andcoil elongation are maintained by application of an external clip 50.Syringe 167 containing the bio-chemical agents 152 is then connected tothe bio-chemical injection port 164. An adequate amount of the agent(s)is injected into the site at tissue tract 47. The bio-chemical agents152 promote and accelerate the hemostatic process. After injection ofthe bio-chemical agents 152, enough time is given for the agents toreact with the blood tissue to form coagulum. External clip 50 is thenremoved, expansible member 74 is collapsed, and device 80 is removed.Removal of the device 80 may be followed by a few minutes of manualcompression at the site to close the small hole left in the vessel wall.

Although certain exemplary embodiments and methods have been describedin some detail, for clarity of understanding and by way of example, itwill be apparent from the foregoing disclosure to those skilled in theart that variations, modifications, changes, and adaptations of suchembodiments and methods may be made without departing from the truespirit and scope of the invention. Therefore, the above descriptionshould not be taken as limiting the scope of the invention which isdefined by the appended claims.

1. A method for closing a blood vessel puncture site disposed at adistal end of a tissue tract, the method comprising: introducing aclosure device through the tissue tract; deploying an expansible memberat a distal end of the device within the blood vessel; displacing abio-chemical sealing member disposed proximal the expansible member soas to expose a bio-chemical region or release region of the device; andreleasing at least one bio-chemical agent from the device and into thetissue tract.
 2. The method of claim 1, wherein the sealing member isdisplaced a distance in a range from about 0.1 cm to about 10 cm.
 3. Themethod of claim 1, further comprising deploying a tensioning elementdisposed proximal the expansible member so that the expansible member isseated against a puncture site.
 4. The method of claim 3, whereindeploying the tensioning element and displacing the sealing member iscarried out simultaneously or sequentially.
 5. The method of claim 3,further comprising limiting elongation of the tensioning element.
 6. Themethod of claim 3, further comprising locating and closing the puncturesite in the blood vessel wall with the expansible member.
 7. The methodof claim 6, further comprising positioning the region at a predetermineddistance proximal to the expansible member and blood vessel wall.
 8. Themethod of claim 7, wherein the bio-chemical agent is coated, sprayed,molded, painted, dipped, or deposited at the region.
 9. The method ofclaim 7, further comprising injecting the bio-chemical agent in at leastone delivery conduit in fluid communication with at least one openingdisposed at the region.
 10. The method of claim 7, further comprisinginjecting the bio-chemical agent in at least one delivery conduit influid communication with a porous release region.
 11. The method ofclaim 1, wherein the bio-chemical agent comprises a clot promoting orvaso-constricting agent.
 12. The method of claim 11, wherein thebio-chemical agent is released for a time period in the range from about0.1 minute to about 15 minutes.
 13. The method of claim 11, furthercomprising re-hydrating the bio-chemical agent with fluid in the tissuetract so as to generate coagulum.
 14. A device for closing a bloodvessel puncture site disposed at a distal end of a tissue tract, thedevice comprising: a shaft having a proximal end and a distal end, theshaft being configured to advance through the tissue tract; anexpansible member disposed on the distal end of the shaft and beingdeployable within the blood vessel; a bio-chemical sealing memberslidably disposed over the shaft and proximal the expansible member; anda bio-chemical region or release region disposed under the sealingmember.
 15. The device of claim 14, further comprising a tensioningelement slidably disposed over the shaft and under the sealing memberproximal the expansible member, wherein the tensioning element seats theexpansible member against the puncture site.
 16. The device of claim 15,wherein the region is positionable at a predetermined distance proximalto the expansible member and blood vessel wall.
 17. The device of claim16, wherein the predetermined distance is in a range from about 0 mm toabout 20 mm.
 18. The device of claim 16, wherein the region has a lengthin a range from about 1 mm to about 100 mm.
 19. The device of claim 16,wherein the region includes at least one bio-chemical agent disposed onthe distal end of the shaft proximal the expansible member.
 20. Thedevice of claim 16, wherein the region includes at least onebio-chemical agent disposed on the tensioning element.
 21. The device ofclaim 16, further comprising an expansible feature disposed on thedistal end of the shaft proximal the expansible member, wherein theregion includes at least one bio-chemical agent associated with theexpansible feature.
 22. The device of claim 16, further comprising atleast one delivery conduit disposed over the shaft and under thetensioning element, wherein the release region includes at least oneopening in fluid communication with a distal end of the at least onedelivery conduit proximal the expansible member.
 23. The device of claim16, further comprising at least one delivery conduit disposed over theshaft and under the tensioning element, wherein the release regionincludes at least one porous member in fluid communication with a distalend of the at least one delivery conduit proximal the expansible member.24. The device of claim 22 or 23, further comprising an injection portin fluid communication with the at least one delivery conduit.
 25. Thedevice of claim 15, further comprising a spacer element disposed betweenthe sealing member and the tensioning element.
 26. The device of claim14, further comprising a handle on a proximal end of the shaft and asafety seal between the handle and the sealing member.
 27. The device ofclaim 14, wherein the sealing member has a length in a range from about0.1 cm to about 100 cm and a diameter in a range from about 0.5 mm toabout 5 mm.
 28. The device of claim 14, wherein the region includes abio-chemical agent comprising a clot promoting or vaso-constrictingagent.